FASLODEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FASLODEX (FASLODEX).
FASLODEX (fulvestrant) is an estrogen receptor (ER) antagonist that binds to ERs with high affinity, downregulates ER protein levels, and inhibits estrogen signaling via both AF-1 and AF-2 domains, thereby blocking cell proliferation in ER-positive breast cancer cells.
| Metabolism | Primarily hepatic via CYP3A4; metabolism involves biotransformation to active metabolites (fulvestrant sulfone, fulvestrant sulfoxide, and others). |
| Excretion | Primarily hepatic metabolism followed by biliary excretion; less than 1% excreted unchanged in urine; fecal elimination accounts for approximately 90% of the administered dose. |
| Half-life | Terminal elimination half-life is approximately 50 days (range 40–60 days) following intramuscular administration, reflecting slow release from the depot and enterohepatic recirculation. |
| Protein binding | 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 10–20 L/kg, indicating extensive tissue binding and distribution into extravascular compartments, including breast and uterine tissues. |
| Bioavailability | Intramuscular: 100% (not applicable for other routes as it is only administered intramuscularly). |
| Onset of Action | Intramuscular: Clinical effects (e.g., estrogen receptor downregulation) detectable within 1–2 weeks; maximal suppression of estradiol-mediated effects achieved after 3–6 months. |
| Duration of Action | Intramuscular: Duration of action persists for at least 1 month after a single 500 mg dose, with sustained estrogen receptor antagonism for up to 6 months; repeated dosing at 2-week intervals maintains continuous blockade. |
| Action Class | Estrogen receptor antagonist |
| Brand Substitutes | Fulveser Injection, Celvestrant PFS Injection, Fulvira 250mg Injection, Fulviglen 250mg Injection, Faslomax 250mg Injection |
500 mg intramuscularly on days 1, 15, 29, and then once monthly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >= 30 mL/min). Not studied in severe impairment (CrCl < 30 mL/min). |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe impairment (Child-Pugh B or C) due to limited data. |
| Pediatric use | Safety and effectiveness not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included patients aged 65 and older with no differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FASLODEX (FASLODEX).
| Breastfeeding | Not recommended. No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Given potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 1 year after last dose. |
| Teratogenic Risk | Category X. FASLODEX is contraindicated in pregnancy and can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action (estrogen receptor antagonist), there is a risk of pregnancy loss and fetal malformations. No adequate studies in pregnant women; animal studies show reproductive toxicity including embryo-fetal lethality and skeletal anomalies. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to fulvestrant or any component of the formulation","Pregnancy (can cause fetal harm)"]
| Precautions | ["Increased risk of thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism)","Hepatic impairment (use with caution; dose adjustment not required for mild-to-moderate impairment)","Injection site reactions (e.g., pain, inflammation, hematoma)","Bone marrow suppression (when used in combination with CDK4/6 inhibitors; monitor blood counts)","Fetal harm (if used during pregnancy; confirm pregnancy status before initiation)","Hypersensitivity reactions (including angioedema and urticaria)"] |
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| Fetal Monitoring | Pregnancy testing should be performed prior to initiation in women of reproductive potential. Contraception must be used during treatment and for 1 year after last dose. Monitor for signs of fetal distress if inadvertent exposure occurs (though contraindicated). No specific fetal monitoring recommended if not pregnant; liver function tests and INR should be monitored in patients on anticoagulants. |
| Fertility Effects | Based on animal studies and mechanism, FASLODEX may impair fertility in females and males. In female rats, decreased fertility and increased preimplantation loss were observed. In humans, potential for reversible or irreversible impairment of spermatogenesis and ovulation due to estrogen receptor blockade. |